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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 37 records · Page 2Linked to original sources

Overt albuminuria predicts diabetic retinopathy in Hispanics with NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) occurs with a higher frequency in Hispanic as compared with non-Hispanic whites. It also appears that there is a higher prevalence of diabetic nephropathy in the Hispanic population when compared with non-Hispanic whites. In the current study, 144 Hispanics and 671 non-Hispanic white NIDDM subjects were studied to determine the possible association of various risk factors and diabetic complications, including overt albuminuria, with diabetic retinopathy. Stereoscopic retinal fundus photographs were obtained and graded by the University of Wisconsin Fundus Photographic Reading Center. We also sought to determine whether risk factors for retinopathy vary between Hispanics and non-Hispanic whites. In the total group, duration of diabetes, glycosylated hemoglobin, neuropathy, diastolic hypertension, use of insulin, and Hispanic ethnicity correlated with the presence of retinopathy. Controlling for severity and duration of diabetes, Hispanics had a significantly increased risk of retinopathy relative to non-Hispanic whites (OR = 2.13, 95% CI = 1.34, 3.37, P = 0.0013). Duration of diabetes and presence of neuropathy were significantly correlated with the presence of diabetic retinopathy in Hispanics and non-Hispanic whites. The presence of overt albuminuria (>200 microg/min), although not related to diabetic retinopathy in non-Hispanic whites, conferred a high risk for diabetic retinopathy in Hispanics (OR = 11.14, CI = 1.20, 103.39, P = 0.0339) independent of other risk factors. In summary, Hispanics with NIDDM have an increased prevalence of diabetic retinopathy when compared with non-Hispanic whites. In addition, overt albuminuria in the Hispanic subjects appears to be a powerful predictor of the diabetic retinopathy.

Albuminuria

Influence of the postoperative period and surgical procedure on ambulatory blood pressure-determination of hypertension load after successful surgical repair of coarctation of the aorta.

AIMS: This study quantified hypertension load using 24-h ambulatory blood pressure monitoring after successful repair of coarctation of the aorta less than (1) or more than 10 years previously (2) and examined the influence of the surgical procedure (anastomosis or subclavian flap). METHODS AND RESULTS: Ambulatory blood pressure recordings were obtained using an Accutracker II monitor every 30 min during the day and hourly, at night. Day and night systolic and diastolic values were higher in coarctation of the aorta than in controls: (day: systolic blood pressure/diastolic blood pressure: 133/71 +/- 6/4 vs 115/66 +/- 3/2 night: systolic blood pressure/diastolic blood pressure: 117/61 +/- 4/4 vs 107/57 +/- 3/2 mmHg, P < 0.01) and at all times, were higher in coarctation of the aorta (2) than in coarctation of the aorta (1). Clinical daytime systolic hypertension was observed in 20% of recordings from coarctation of the aorta (1) and 49% from coarctation of the aorta (2) while diastolic hypertension was not observed. However, systolic blood pressure and diastolic blood pressure responses to daily activities were significantly higher in coarctation of the aorta than in controls and this was more marked in coarctation of the aorta (2) than in coarctation of the aorta (1). Type of surgery did not affect either hypertension prevalence or blood pressure reactivity. CONCLUSIONS: These observations indicate exaggerated systolic blood pressure and diastolic blood pressure reactivity after repair of coarctation of the aorta, the prevalence of systolic hypertension doubling 10 years after surgery.

Adolescent

Measuring the ability to meet family needs in an intensive care unit.

OBJECTIVE: To measure the ability to meet family needs in an intensive care unit (ICU). DESIGN: Descriptive survey. SETTING: University hospital ICU. SUBJECTS: Ninety-nine next of kin respondents and 16 secondary family respondents were recruited. INTERVENTIONS: A modified Society of Critical Care Medicine Family Needs Assessment instrument was used. MEASUREMENTS AND MAIN RESULTS: Demographic variables included patient age, gender, diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission, Therapeutic Intervention Scoring System (TISS) score on the date of interview, cumulative TISS of the ICU on the day of interview, number of patients in the ICU at time of interview, nurse/patient ratio for the patient, average nurse/patient ratio of the entire unit, day of the week of the interview, timing of the interview, number of ICU attending physicians who cared for this patient (scheduled for a period of seven consecutive days), number of nurses who cared for the patient, if a nurse was assigned the same patient on two consecutive days worked, length of stay in the ICU, and length of hospital stay. Demographic information concerning the family member included gender, age, commuting time to the hospital, visiting time in the hospital per day, number in family group, relationship to the patient, ethnic background, and education level. The additive score of all questions in the needs assessment instrument was calculated and used as the dependent variable. The independent variables were demographic information concerning patients, ICU, and respondents. The model coefficient of determination (R2adj) was 0.20 with a p = .0079. Greater family dissatisfaction (i.e., higher score) was present if there were more than two ICU attendings per patient (p = .048), or if the same nurse was not assigned on two consecutive days (p = .044). Family satisfaction increased if the respondent was female (p = .006), if the patient had a higher APACHE II score (p = .007), and if the patient's relationship with the most significant family member was brother/sister (p = .012). The family needs instrument was reliable and demonstrated a high degree of concordance with a second respondent in the same family surveyed. CONCLUSIONS: Communication by the same provider was important when measuring the ability of an ICU to meet family needs. Instrument scores and the ability to meet family needs differed depending on the gender and the relationship to the patient of the most significant family member. We speculate that this instrument may be a useful adjunct in assessing quality of critical care services provided.

APACHE

Changes in treatment and outcomes of children receiving care in the intensive care unit for severe acute asthma.

OBJECTIVE: Significant changes have occurred in the intensity of treatment of children with severe asthma in the last decade. The objectives of this study are 1) to describe the changes in treatment of asthmatic children needing care in the intensive care unit (ICU) initially treated in our emergency department (ED) in 1983 to 1985 (I) and in 1990 to 1992 (II), and 2) to examine if these changes correspond to changes in clinical outcomes. DESIGN: Retrospective descriptive study. PATIENTS: All asthmatic children less than 18 years old treated in the ED and admitted to the ICU directly or via the ward with a primary diagnosis of asthma. SETTING: Pediatric tertiary care hospital. RESULTS: A total of 89 ICU admissions were required for patients initially treated in our ED, 54 in 1983 to 1985 and 35 in 1990 to 1992. In 1985, 29.7% of asthma patients required hospital admission and 0.5% needed ICU admission, while 30.7 and 0.7% required hospital and ICU admission, respectively, in 1992. Admissions to the ICU directly via the ED were similar in both time periods (I, 27; II, 30), while those admitted to the ICU via the ward decreased significantly (I, 27; II, 5; P < 0.01). Recently, while in the ED, these ICU patients, on average, were treated with < or =q1h albuterol inhalations longer (I, 1.7 hours; II, 3.4 hours; P < 0.001), more frequently (I, 1.8 inhalations/h; II, 3.3 inhalations/h; P < 0.001), and with greater dosages (I, 0.20 mg/kg/h; II, 0.55 mg/kg/h; P < 0.001), than previously. Only 72% of patients in 1983 to 1985 received i.v. steroids in the ED versus 100% in 1990 to 1992. Ward patients in 1990 to 1992 received < or =q1h inhalations for a greater proportion of their ward stay (I, 6.9/14.7 hours = 47%; II, 9.2/9.2 hours = 100%). There was a recent trend toward longer ICU treatment with < or =q1h albuterol inhalations (I, 8.7 hours; II, 12.3 hours; P = 0.24) and with i.v. albuterol (I, 29.4 hours; II, 37.4 hours; P = 0.26). Ventilation rates were low (I, 5/54 = 9.3%; II, 2/35 = 5.7%; P = NS) and the average duration of ICU stay remained unchanged (I, 40.6 hours; II, 42.1 hours; P = NS). CONCLUSIONS: Despite recent dramatic ED and ward treatment changes, ICU admission rates for pediatric asthma remain relatively constant. However, intensive treatment may have contributed to the decrease in ICU admissions via the ED to ward route in slightly less critical cases.

Acute Disease

Using social network and ethnographic tools to evaluate syphilis transmission.

BACKGROUND AND OBJECTIVES: Partner notification has been the cornerstone for the prevention and control of syphilis in the United States. This technique may not make full use of contextual data that an ethnographic and social network approach can offer. GOALS OF THE STUDY: The occasion of a syphilis outbreak among young people was used to investigate the applicability of a social network approach and to test the validity of several traditional approaches to syphilis epidemiology. STUDY DESIGN: An outbreak of syphilis was investigated by interviewing both infected and noninfected people, by directing resources based on network association, by creating and evaluating network diagrams as an aid to the epidemiologic process, and by including ethnographic observations as part of outbreak management. RESULTS: Diagrammatic display of network growth provided a useful alternative to the traditional epidemic curve. Case prevention was demonstrated by identifying uninfected people with multiple concurrent exposures. Concurrent, overlapping exposure in infected people rendered traditional "source" and "spread" criteria moot. CONCLUSIONS: The current discussions of partner notification may be informed by recognizing that it is a subset of a broader and potentially more powerful approach. This approach calls some basic tenets of syphilis epidemiology into question.

Adolescent

Detection of ventricular fibrillation by transvenous defibrillating leads: integrated versus dedicated bipolar sensing.

INTRODUCTION: Dedicated bipolar sensing has been suggested to be safer than integrated bipolar sensing due to an increased incidence of failure to redetect ventricular fibrillation after an unsuccessful shock with leads that use integrated bipolar sensing. We compared sensing characteristics during ventricular fibrillation of simultaneously recorded dedicated and integrated bipolar electrograms. METHODS AND RESULTS: Thirty patients undergoing transvenous defibrillator implantation with a Transvene lead were studied. Simultaneous recordings were made from the dedicated bipole and the integrated bipole from the distal tip to the coil (interelectrode distance 18.3 mm). The mean detection time and number of undetected beats for the initial episode of ventricular fibrillation were 2804 +/- 569 msec and 0.9 +/- 0.8 using the dedicated recordings and 2938 +/- 546 msec and 1.4 +/- 1.1 (P = 0.026) using the integrated recordings. The mean redetection times and number of undetected beats following a failed first shock (n = 13) were 2468 +/- 225 msec and 0.8 +/- 1.1 for the dedicated recordings and 3042 +/- 498 msec (P < 0.0003) and 4.2 +/- 4.2 (P < 0.005) for the integrated recordings. Frequency analysis of the ventricular fibrillation electrograms demonstrated that the signal energy in the dedicated electrograms was significantly greater than the energy in the integrated electrograms (P < 0.0001). There was a significant negative relationship between detection times and the ventricular fibrillation signal energy. There was no independent effect of recording type (dedicated versus integrated). CONCLUSION: There are only minor differences in detection/redetection of ventricular fibrillation between dedicated and integrated (with tip to coil spacing of 18.3 mm) recording configurations. Detection times during ventricular fibrillation are related to the signal variance or energy recorded. Differences in the sensing performance of the two recording configurations can be explained by the differences in signal energy between the dedicated and integrated recordings that occur during ventricular fibrillation.

Defibrillators, Implantable

Amphotericin B colloidal dispersion combined with flucytosine with or without fluconazole for treatment of murine cryptococcal meningitis.

Studies with animals and in vitro studies have demonstrated that flucytosine plus amphotericin B or fluconazole has significantly improved mycologic activity against meningitis caused by Cryptococcus neoformans compared to the activity of amphotericin B or fluconazole used alone. However, few doses have been tested in combination. This study evaluated the antifungal efficacy of amphotericin B colloidal dispersion (ABCD) combined with flucytosine with and without fluconazole in a murine model of cryptococcal meningitis. The following dosages were tested: ABCD at 0 to 12.5 mg/kg of body weight given intravenously 3 days/week, flucytosine at 0 to 110 mg/kg/day, and fluconazole at 0 to 50 mg/kg/day. Meningitis was established in male BALB/c mice by intracerebral injection of C. neoformans. Treatment with flucytosine with or without fluconazole dissolved in the sole source of drinking water was started on day 2; animals were sacrificed at 16 days, and the numbers of fungal colonies in the brain were quantified. A survival rate of 100% was achieved with ABCD plus flucytosine without fluconazole; however, the addition of fluconazole was required to prevent weight loss (P < 0.00001) and to achieve the maximum antifungal effect (P < 0.00001). The only region of dose combinations for which the 99% confidence intervals were less than 100 CFU/g of brain was defined by ABCD at 5.0 to 7.5 mg/kg combined with flucytosine at 20 to 60 mg/kg/day and fluconazole at 30 to 40 mg/kg/day. The triple combination of ABCD plus flucytosine and fluconazole was necessary to achieve the greatest antifungal activity.

Amphotericin B

Carbamazepine interference with an immune assay for tricyclic antidepressants in plasma.

BACKGROUND: Drug toxicological screening is commonly used as a diagnostic tool in patients with suspected toxic ingestion. False positive results due to cross-reactive compounds in drug assays may lead to misdiagnosis and mismanagement, especially when child abuse is suspected. CASE REPORT: Two of our patients with history of ingestion of carbamazepine were tested positive on screening with the tricyclic antidepressant immunoassay. The immunoassay's known cross-reactivity for carbamazepine is reportedly as low as 0.3%. Plasma samples of our patients were initially considered positive for tricyclic antidepressants because the cross-reaction of carbamazepine gave tricyclic antidepressant concentrations as imipramine equivalent sufficiently above the assay cut-off point (20 ng/mL). Later, confirmatory urine testing of both patients using high-performance liquid chromatography was negative for tricyclic antidepressants. CONCLUSION: This interference has significant clinical implications, and can be avoided on urine testing using a specific chromatographic assay such as high-performance liquid chromatography.

Adolescent

Criteria used by clinicians to differentiate sinusitis from viral upper respiratory tract infection.

BACKGROUND: Acute sinusitis and upper respiratory tract infections (URIs) share many common symptoms and signs. Objective criteria have been identified that are valid for distinguishing between these two clinical problems. The objective of this study was to determine how often clinicians use these validated criteria and how often they rely on clinical cues that are less valuable for differentiating sinusitis from URI. METHODS: We performed a retrospective review of 734 patients with a diagnosis of acute sinusitis (n = 367) or URI (n = 367) at a family practice residency training site over a 3-year period. Charts were reviewed to ascertain patient demographics, past history, current symptoms, physical findings, and treatment prescribed. RESULTS: Patients with sinusitis were likely to be older, female, smokers, have a history of allergic rhinitis, and have longer symptom durations. Complaints of sinus pressure or discolored nasal discharge and the finding of sinus tenderness were strongly associated with the diagnosis of sinusitis. In multivariate analysis, eight factors were independently associated with the diagnosis of sinusitis. Four clinical cues alone (sinus tenderness, sinus pressure, postnasal drainage, and discolored nasal discharge) were highly associated with the diagnosis of sinusitis and explained 60% of the variation in the diagnosis between sinusitis and URI. CONCLUSIONS: Physicians tend to rely on four factors to differentiate sinusitis from URIs. Only one of these has been shown to be a reliable predictor of acute sinusitis. This use of unreliable criteria may lead to misdiagnoses and inappropriate prescriptions for antibiotics.

Acute Disease

Effects of intravenous propranolol on human ventricular strength interval curves.

BACKGROUND: Prior studies on the effects of propranolol on human ventricular refractoriness have yielded occasionally inconsistent results. Most prior studies have examined refractory periods at a single stimulus intensity and without using continuous pacing; thus, the effects of propranolol on repolarization may have not been completely defined. The purpose of the present study was to reevaluate the effects of beta blockade on the human ventricular effective refractory period. METHODS: Strength-interval curves were performed in duplicate in a group of 10 patients to demonstrate their reproducibility. Strength-interval curves were performed before and after intravenous propranolol administration in a second group of 10 patients who had no evidence of structural heart disease. RESULTS: Propranolol increased the absolute refractory period from 208 +/- 9 milliseconds to 212 +/- 10 milliseconds (p = 0.01). However, propranolol decreased the coupling interval at which the strength-interval curve began to show an increase in the stimulus intensity required for capture from 236 +/- 8 milliseconds to 232 +/- 9 milliseconds. This resulted in a decrease of the width of the strength-interval curve from 28.0 +/- 5.1 milliseconds to 20.4 +/- 5.5 milliseconds (p < 0.005). Propranolol also significantly increased the slope of a logarithmic fit of the strength-interval curves. CONCLUSION: Propranolol exerts complex effects on human ventricular refractoriness. Propranolol decreases the width and increases the slope of human strength-interval curve, rather than increasing or decreasing the refractory period. These results have potential implications for antiarrhythmic effects of propranolol.

Adrenergic beta-Antagonists

Irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer.

During the 1980s, platinum-based regimens were yielding response rates typically less than 25%, median survival durations of about 25 weeks, and 1-year survival rates less than 25% in patients with advanced non-small-cell lung cancer (NSCLC). Currently, results from single institution phase II trials of agents introduced in the 1990s show a doubling of these numbers, and results from multiinstitutional trials are demonstrating response rates ranging from 30% to 40%, median survival durations of 40 weeks, and 1 year survivals of 40%. Single agent irinotecan shows significant activity against NSCLC in preclinical and early phase I/II clinical studies, with activity similar to that for other new agents. Therapeutic synergy is observed in preclinical tumor models when irinotecan and cisplatin are combined, and phase I/II trials of this combination have demonstrated response rates > or = 50%. Herein the author provides an overview of data from phase II trials of irinotecan and focuses on preliminary results of a large US multicenter phase II trial of weekly irinotecan plus monthly cisplatin in 52 patients with advanced NSCLC. A response rate of 28.9% (95% CI, 16.5%-41.2%) and a median survival of 9.9 months were observed in this trial. US studies to design a more optimal irinotecan/cisplatin regimen in the same patient population are ongoing, and early results are encouraging.

Antineoplastic Agents

Expression of beta-catenin, alpha-catenin, and E-cadherin in Barrett's esophagus and esophageal adenocarcinomas.

Loss of expression and function of the E-cadherin/catenin membrane complex can result in loss of cell adhesion and contribute to invasive or metastatic potential in carcinomas. The aim of this study was to examine the expression of alpha- and beta-catenin and E-cadherin in Barrett's esophagus with and without dysplasia and in esophageal adenocarcinomas and to identify any relationship with tumor growth pattern and clinical outcome. Immunoperoxidase staining for alpha- and beta-catenin and E-cadherin was performed on specimens of Barrett's esophagus with and without dysplasia and on 54 esophageal adenocarcinoma specimens. Membranous staining for all of the components was seen in normal gastric and esophageal mucosa. Abnormal expression of beta-catenin, alpha-catenin, and E-cadherin was significantly associated with higher degrees of dysplasia in Barrett's esophagus. Fourteen of 16 cases of high grade dysplasia and 7 of 7 cases of intramucosal carcinoma showed abnormal expression of beta-catenin, compared with 3 of 6 cases indefinite for dysplasia and 11 of 17 cases with low grade dysplasia (P = 0.022). Similar results were seen for expression of alpha-catenin (P < .01) and E-cadherin (P = .049). In esophageal adenocarcinomas, preserved expression of these proteins occurred more frequently in well-differentiated tumors; abnormal expression was more common in diffusely infiltrative poorly differentiated tumors that did not form glands. Focal nuclear staining for beta-catenin was present in two high-grade dysplasias, two intramucosal carcinomas, and five adenocarcinomas. No survival advantage was demonstrated for patients whose tumors retained expression of these cell adhesion components. In conclusion, abnormal expression of the E-cadherin/catenin membrane complex is common in esophageal adenocarcinoma and occurs early in the dysplasia/carcinoma sequence in Barrett's esophagus, indicating that disturbances in this cell adhesion complex might be important in tumorigenesis and tumor progression in this disorder.

Adenocarcinoma

Detection of medulloblastoma and astrocytoma-associated ganglioside GD3 in cerebrospinal fluid.

Shedding of gangliosides by tumor cells may enhance tumor development. We recently showed that cells of the human brain tumor, medulloblastoma, shed gangliosides in vitro and have therefore examined ganglioside shedding by pediatric brain tumors into the cerebrospinal fluid (CSF). GD3, a major ganglioside in medulloblastoma and astrocytoma, was the target for detection in the CSF by immunostaining using the monoclonal antibody R24 and enhanced chemiluminescence detection. Mean CSF GD3 levels in patients with medulloblastomas (n = 9) and astrocytomas (n = 10) were significantly higher than those of controls (mean +/- SD 44.7 +/- 8.4 versus 18.2 +/- 1.9 pmol/ml, n = 20, P < 0.0002). Mass spectrometric analysis showed that tumor-derived ganglioside GD3 contained heterogeneous ceramide structures and, interestingly, the ceramide subspecies with shorter fatty acyl chains were selectively shed. The elevated CSF GD3 concentrations in patients with medulloblastoma and astrocytoma support the concept that ganglioside shedding, which may have significant biological consequences, is characteristic of human brain tumors.

Astrocytoma

Proteinase-mediated insect resistance to Bacillus thuringiensis toxins.

Two Bacillus thuringiensis (Bt)-resistant strains of the Indianmeal moth, Plodia interpunctella, lack a major gut proteinase that activates Bt protoxins. The absence of this enzyme is genetically linked to larval survival on Bt-treated diets. When considered with previous data supporting the existence of receptor-mediated insect resistance to Bt, these results provide evidence that insect adaptation to these toxins occurs through multiple physiological mechanisms, which complicate efforts to prevent or manage resistance to Bt toxins in insect control programs.

Animals

Identification of the regions on the M110 subunit of protein phosphatase 1M that interact with the M21 subunit and with myosin.

We have previously isolated a form of protein phosphatase-1 (PP1M) from avian smooth muscle myofibrils that is composed of the catalytic subunit of PP1 (PP1C) bound to an M-complex consisting of 110-kDa (M110) and 21-kDa (M21) subunits. The interaction of PP1C with an N-terminal region of the M110 subunit enhances the dephosphorylation of myosin and suppresses the dephosphorylation of other substrates [Alessi, D. R., MacDougall, L. K., Sola, M. M., Ikebe, M. & Cohen, P. (1992) Eur. J. Biochem. 210, 1023-1035; Chen, Y. H., Chen, M. X., Alessi, D. R., Campbell, D. G., Shanahan, C., Cohen, P. & Cohen, P. T. W. (1994) FEBS Lett. 356, 51-56; Johnson, D. F., Moorhead, G., Caudwell, F. B., Cohen, P., Chen, Y. H., Chen, M. X. & Cohen, P. T. W. (1996) Eur. J. Biochem. 239, 317-325]. In this paper, we establish that PP1M accounts for nearly all the myosin phosphatase activity in myofibrils, that the M110 and M21 subunits are present at similar concentrations in the myofibrillar fraction, and that these subunits are entirely bound to PP1. We demonstrate that the M21 subunit does not interact with PP1C, but with the C-terminal 72 residues of the M110 subunit, a region which is 43% identical to residues 87-161 of the M21 subunit. A fragment of the M21 subunit, M21-(M1-L146), which lacks the C-terminal leucine zipper, also bound to the M110 subunit, but two other fragments M21-(M1-E110) and M21-(E110-K186) did not. The M110 and M21 subunits were both found to be myosin-binding proteins. The C-terminal 291 residues of the M110 subunit, but not the C-terminal 72 residues, bound to myosin, but the N-terminal fragments M110-(M1-E309) and M110-(M1-S477) did not. Thus, the region of the M110 subunit that stimulates the dephosphorylation of myosin by PP1C is distinct from the region that targets PP1M to myosin. Remarkably, each myosin dimer was capable of binding about 20 mol M21 subunit and many of the M21-binding sites were located in the myosin rod domain. The potential significance of this observation is discussed.

Amino Acid Sequence